The long-term objective of this Career Development Award to Promote Diversity in Neuroscience Research is to develop the candidate's skills in applying novel brain network approaches to the study of neurodevelopmental disorders, and in conducting clinical assessments, so that she can become an independent investigator in the fields of neuroimaging and autism research. Specifically, the candidate will develop expertise in using diffusion tensor imaging (DTI) data in conjunction with recently developed multivariate pattern classification and effective connectivity analyses of functional magnetic resonance imaging (fMRI) data to examine structural and intrinsic functional brain connectivity underlying atypical behavior and cognition in children with autism spectrum disorders (ASD). To this end, the candidate will be mentored and trained by experts in the fields of neuroimaging, engineering, clinical psychology, neurology and psychiatry. The candidate will also gain critical experience in clinical assessments necessary for successfully working with children with ASD. In addition, the candidate will undertake formal coursework and attend seminars in functional neuroimaging, clinical psychology, and computer programming to achieve this goal. The research project proposed by the candidate will enable the acquisition of the skills required to become a successful independent investigator in the field of developmental cognitive neuroscience. ASD is a complex neurodevelopmental disorder of largely unknown etiology, characterized by social communicative impairments, restricted interests, and repetitive and stereotyped behaviors. The main goal of the proposed research is to examine aberrant structural and functional brain connectivity underlying atypical cognition and behavior in children with ASD. The candidate proposes to probe large-scale brain networks using DTI and fMRI to examine possible aberrant cortical connectivity and compromises in dynamic interactions between networks in children with ASD. She will specifically test a novel systems-level hypothesis she has put forth, synthesizing recent advances in brain network connectivity with converging evidence from neuroimaging studies in autism. The hypothesis is that hypoactivity of the anterior insula during processing of social stimuli results in reduced salience detection in individuals with ASD, which impairs dynamic switching between other large-scale brain networks important for cognition. Additionally, she will explore methods to establish brain-based biomarkers to distinguish children with ASD from typically developing children using a combination of brain connectivity measures and cognitive and behavioral measures. Completion of this research project and training plan will enable Dr. Uddin to gain proficiency relevant to her goal of becoming an independent investigator in the fields of autism and neuroimaging research, and will also facilitate the principled development of biomarkers of brain network dysfunction in ASD. This Career Development Award is consistent with the NIH goals to promote diversity in neuroscience research. ) PUBLIC HEALTH RELEVANCE: Autism spectrum disorders (ASD) affect 1:150 individuals, and the incidence continues to rise steadily, making the disorder an urgent public health concern. ASD results in lifelong difficulties for afflicted individuals and their families, and there is no known cure. Recently developed analytic tools have enabled the study of brain connectivity in vivo, revealing important principles of brain organization in individuals with ASD. Characterization of the integrity and functional roles of brain networks, as well as interactions between them, will help us to understand the underlying brain differences in individuals with ASD and eventually lead to the development of more effective treatments and therapies. )